Background
Congenital Type 1 myotonic dystrophy (CDM1) is a rare genetic disorder, with no current disease-modifying treatments. AMO-02/tideglusib is an orally available GSK3β inhibitor in Phase 2 clinical development for CDM1.
Objectives
Data are presented from the ongoing REACH CDM X clinical trial (NCT05004129), that has enrolled 65 participants between 6 and 45 y.o. (NCT05004129, the REACH CDM X Study). The trial has been expanded to include participants with childhood onset myotonic dystrophy as well as adults with CDM1.
Approach
A weight-adjusted oral dose of 1000 mg has been administered once daily in an open-label manner to participants that completed the preceding REACH CDM1 Study (NCT03692312) or that were treatment-naïve. The participants have been clinically evaluated on a regular basis. Serial safety and tolerability data (i.e. vital signs, laboratory and ECG assessments, and adverse events reports) have been collected, along with efficacy data. This data has been reviewed on a quarterly basis by an independent Data Safety Monitoring Committee.
Results
No protocol modifications have been recommended by the Committee. Most participants have already completed two years of treatment, and only 10.7% of enrollees have discontinued from the trial. There has been no pattern of safety or tolerability issues (including no serious adverse events related to AMO-02/tideglusib), with the caveat that approximately 15% of participants have experienced protocol-defined transient increases in transaminase (ALT, AST) values. Clinical benefit has been evident in the majority of participants, with improvements evident in domains such as ambulation, cognition, gastrointestinal functioning, and activities of daily living. Serial Clinical Global Impression – Improvement scores have reflected this holistic pattern of efficacy.
Conclusions
The data from this ongoing Phase 2 study suggests that AMO-02/tideglusib has the potential to be a useful treatment for individuals affected by early-onset Type 1 myotonic dystrophy. Additional studies are planned to confirm these impressions.